EP0787523B1 - Apparatus and process for material-specific treatment of fluids - Google Patents

Abstract

Fluid treatment element comprises (a) a housing having fluid supplied to an inlet, an outlet for the treated fluid and an element which incorporates porous semi-permeable membranes around a hollow chamber (2) whose open end is directed towards the outlet; (b) a continual passage is formed by the element, between the inlet and the outlet ; (c) a primary current formed from the fluid under treatment (4) flows around the element, a part of this primary flow forms a secondary flow (5) through the porous membrane wall which then collects in the hollow chamber (2) and leaves the treatment element to again join the primary flow (4) within the housing.

Description

The invention relates to a device and a method for substance-specific treatment of a fluid through interaction with target substances contained in the fluid to be treated.

Under fluids in the sense of the present invention, gases, Gas mixtures, gases loaded with particles and in general Liquids such as understood clear solutions or suspensions.

Substance-specific treatments for fluids are increasing Significance of importance in application areas such as Biotechnology, medicine or chemical technology. Examples of this are the extraction of active substances from Cell suspensions in which genetically modified cells like substances Antibodies, hormones, growth factors or enzymes in most have produced small concentrations. An important application is also the extracorporeal removal of unwanted Substances from human blood. Finally is a wide application also the catalytic or biocatalytic - enzymatic - treatment of liquids such as. the hydrolysis of oils by lipases, which on a Matrix are immobilized. In many treatment applications These liquids contain a wide variety of particles Type, i.e. they are available as suspensions.

The substance-specific treatment of fluids is often carried out in such a way that the fluid to be treated is brought into contact with a carrier material on and / or in which interacting groups or substances are immobilized in a specific, selective manner with the target substance contained in the fluid, ie interact with the substance to which the substance-specific treatment is directed. Such interactions can be, for example, cation or anion exchange, hydrophilic-hydrophobic interaction, hydrogen bonding, affinity or enzymatic or catalytic reactions and the like. In the affine separation of substances, ligands are coupled to the carrier material or immobilized in the carrier material, which have the function of specifically binding an individual target substance or an entire class of substances by adsorption. This target substance is called a ligate. An example of class-specific ligands are positively charged diethylaminoethyl (DEAE) groups or negatively charged sulfonic acid (SO ₃ ) groups, which adsorb the class of positively charged or negatively charged molecules. Specific ligands are, for example, antibodies against a specific protein which is bound to the antibody as a ligate.

Essential criteria for substance-specific treatment of fluids are productivity and selectivity. With a view on productivity it is important that as many as possible substance-specific groups per volume unit are available stand with the contained in the fluid to be treated Target substance can interact. At the same time, the transport of the target substance is maximized to the substance-specific groups or substances desirable.

A commonly used in affinity chromatography Carrier material for ligands are Sepharose particles to which the ligands are coupled and in the form of a bed be present in a chromatography column. Even though a high concentration of ligands with high selectivity productivity is well known low because of the compressibility of the Sepharose particles the throughput through the column remains relatively low got to. In addition, the access of the ligates to those in the Diffusion-controlled ligands containing Sepharose particles, whereby especially when separating larger molecules such as of proteins because of them low diffusion rates, long residence times and thus only low throughputs and low productivity result.

US-A-4 202 775 discloses one made of porous, rigid polymer particles existing column material that acts as adsorbents be used to separate organic components can, the proteins in aqueous solution are adsorbed. This column material no longer has the disadvantage of compressibility, however Disadvantage of the diffusion-controlled mass transport in the Particles, associated with long dwell times and less Productivity.

In US-A-5 019 270 is a chromatography column material presented from rigid, porous particles, in which a partial flow of the flowing through the chromatography column and liquid to be treated convectively Particles flow through, with those in the porous structure of the interacting groups of particles in contact comes and then again with the flowing around the particles Liquid flow is combined. Because of the convective Mass transport through the particles is opposite to that previously mentioned column materials a reduction in Dwell time and an increase in productivity possible.

There is an advantage to being filled with such particles Chromatography columns that their structure and use very is simple. However, all particulate column materials the disadvantage in common that when treating particles or Liquids containing cells, i.e. suspensions, which Particles of the column material can be chosen to be relatively large need to have a good flow of the particle bed without Retention of particles or e.g. Cells of fluid and without ensuring a deep filtration effect through the bed and to keep the pressure drop low. hereby however, the amount available per volume element is reduced standing amount of substance-specific groups, since the volume occupied by the particles in the column is smaller becomes. In addition, there is an increasing particle size an adverse extension of the residence times.

In the case of such chromatography columns, it is desirable that the Particles are present in an ordered packing in the column, in order to maximize the proportion of particles in the bed and an equalization of the flow between to cause the particles. This can be done in part through use of spherical particles with as uniform as possible Diameter can be achieved. The production of such uniform However, particle is complex. Furthermore leaves generally do not avoid each other with such particle beds, that the flow channels between the particles below fluid dynamic aspects are not optimally designed are. In the gusset areas between the particles it can easily create dead spaces, which in particular negative for the substance-specific treatment of suspensions Phenomena such as the deposition of suspended Particles in the gusset areas between the particles of the Fill can result.

The described disadvantages of particulate carrier materials led to the development of a number of processes substance-specific treatment of fluids in which membranes with porous structure as carrier materials for the interacting Groups are used. Because of their porous Structure, these membranes have a large inner surface available so that to the membranes in a high concentration a large number of functional units per unit volume Groups that can interact with the fluids to be treated flowing through the membrane kick (see e.g. E. Klein, "Affinity Membranes", John Wiley & Sons, Inc., 1991; S. Brandt u. a., "Membrane-Based Affinity Technology for Commercial Scale Purifications ", Bio / Technology Vol. 6 (1988), pp. 779-782).

An adjustment can be made via the design of the membrane used to meet the requirements of the treatment process. There are membranes in the form of hollow fibers or as flat membranes made of different materials, so that an adaptation to the physicochemical properties of the fluids to be treated is possible. Also the pore size the membranes can be adjusted so that the one to be treated Fluid with the target substance contained in it the membrane can flow through convectively and - in the case of Linking the target substance to the interacting groups - no blocking of the membrane occurs.

Due to the thickness of the membrane wall, the residence time of fluids to be treated in the membrane and in the Influence the pressure drop that arises. in this connection membranes stand out due to their usually only slight Wall thickness (e.g. <100 µm) due to short transport routes of the fluids to be treated to the interacting groups, whereby the dwell times are comparatively short. simultaneously arises as a further advantage in use of membranes as carrier material compared to particulate Carrier materials that are due to the essentially uniform thickness of the membrane wall a more uniform Flow through the carrier material and consequently one narrower residence time distribution as well as more even and complete "Use" of the interacting groups results.

There are a number of devices containing such membranes described in the process for substance-specific treatment of fluids are used and in which both flat membranes and hollow fiber membranes are used. It is between the so-called dead-end filtration or the dead-end modules and the to distinguish cross-flow filtration or the cross-flow modules.

In the case of dead-end filtration, the whole is used as a feed stream fluid flowing into the membrane module through the membrane passed through and on the inflow side of the membrane opposite discharge side derived as filtrate or permeate.

When driving in cross-flow mode, the feed stream flows parallel to one side of the membrane. A part occurs of the feed stream through the membrane. The one who stepped through Partial stream is called permeate, which is on the feed stream side remaining partial stream derived as retentate. in this connection can also be an additional on the permeate side of the membrane Fluid flow can be introduced through the membrane passes through partial stream.

US-A-4 935 142 discloses an apparatus for performing this described by affinity separation processes in dead-end mode, which contains stacks of flat membranes. To the flat membranes ligands are coupled to which those from the to be treated Ligates to be separated are bound. The the Membrane stacks of flat membranes are against the surrounding one Sealed housing so that a forced flow through the membrane stack is generated. A disadvantage of such a Structure is the high pressure loss in the flow of the stack, whereby additional measures are also required are sufficient stability to the flat membrane elements against the high pressures that occur.

In EP-A-0 173 500, EP-A-0 280 840 and EP-A-0 610 755 are also devices for use with membrane-based affinity separation methods such. B. the insulation of immunoglobulins, antigens, etc. described. These devices or membrane modules contain a star shape folded, microporous flat membranes. The folded in a star shape Flat membranes are supported between two coarse grids and arranged between two coaxially to each other cylindrical housing elements introduced. Prefers can also have several flat membranes folded in a star shape be arranged concentrically to each other in the housing. Similar constructed modules are described in EP-A-0 662 340, with small particles in the folded flat membrane structure with specifically interacting groups.

The liquid to be treated is in the devices mentioned under pressure from the inside out or in the opposite direction through the module and flows convectively through the membrane in dead-end mode. Compared to modules with unfolded, concentric to each other arranged modules offer the advantage of the modules mentioned a relatively larger membrane area in comparison less pressure loss. However, they are usually only minor Degree of filling, defined as membrane volume based on the total volume of the module, possible.

For all membrane modules to be operated in dead-end mode is disadvantageous that they are for the treatment of particles containing fluids, i.e. e.g. of suspensions, then not are suitable if the particles contained in the fluid in the Order of magnitude of the pore diameter. The particles would lead to the formation of a layer on the membrane wall and block the membrane. For use in e.g. Affinity separation process for particle-containing liquids, i.e. Such dead-end modules can be used for suspensions only in combination with an upstream pre-filtration / pre-cleaning stage operate. hereby However, such a method loses efficiency, for example in that in many cases by such a pre-cleaning much of the target substance is lost.

The disadvantages mentioned in modules operated in dead-end mode in relation e.g. on their usability in suspensions at least partially avoided when using cross-flow modules become. In these can be parallel to the Membrane surface flowing feed stream at sufficiently high Shear stresses build up a layer of suspended Reduce particles.

WO 90/05018 discloses a membrane module for use in the case of affinity separation processes, which consist of building a cross-flow module equivalent. A liquid containing ligate will introduced into the module housing via an inlet device and flows tangentially over one side of one, for example hollow fibrous membrane, coupled to the ligands are. Part of the liquid enters the membrane, flows through this, the ligates to the Ligands are attached and occurs on the entry side opposite membrane side as Permaetstrom. The retentate stream and Permeate stream derived. Essential feature of the according to WO 90/05018 membranes used is an isotropic, microporous Structure that is a convection flow of macromolecules containing solutions.

In US-A-4 266 026 a cross-flow module, the contains anisotropic hollow fiber membranes for a process for Implementation of catalytic reactions described. Both the catalysts used are in particular to enzymes that are in the membrane structure for example are immobilized via coupling reagents. The one to be treated Liquid flows under pressure as a feed stream Lumen of the hollow fibers. Part of the liquid flows through thereby convectively the membrane wall and becomes the catalytic Subject to reaction. As an example, the catalytic Conversion of lactose into glucose and galactose using Galactosidase carried out as a catalyst. Retentate and Permeate are separated from the module as liquid flows dissipated, combined in a storage container and on the lumen side as long as returned to the module in the circuit, until the desired conversion of the reacting substance is reached is.

A modification of a cross-flow process is described in WO 93/02777. For specific removal of certain Components from the blood are used in a U shape in a special way molded case embedded bundle of semi-permeable Hollow fiber membranes that act as plasma filters. The hollow fiber membranes blood flows through the lumenside substance-specific treatment takes place on the membrane separated blood plasma in the outer space around the hollow fiber membranes. In this outdoor space is for attachment of the components to be separated, e.g. immobilized enzymes or cleaning medium containing antibodies. The bundle can basically be in an inflow branch and in an outflow branch divide. Because of in the area of the inflow branch positive transmembrane pressure occurs the diffusion superimposed convective transport of blood plasma through the membrane into the outside space. In the area of Outflow branches flow the treated plasma due to the there negative transmembrane pressure occurring in the lumen of the Hollow fiber membranes back and is reunited with the blood.

The method according to WO 93/02777 offers the advantage that no separate pumps and / or control bodies for the Permeate stream, i.e. the plasma flow are needed. however the modules used have a large dead space in the Outside area of the membranes.

In the device for blood treatment according to EP-A-0 112 094 the permeate is also not used separately from the Module-led out, but within the module again with the retentate, i.e. in this case brought together the blood. The membrane also serves as a plasma separator, with von a channel is formed on one side of the membrane which the blood flows, and from the other side of the membrane and that surrounding housing a treatment room in which there is a material for substance-specific treatment. By a suitable device are pressure variations on the treatment room impressed. This will make the pressure difference periodically changed between the blood channel and the treatment room, that alternately plasma from the blood through the Membrane permeates into the treatment room, where it is the undergoes substance-specific treatment. Subsequently the treated plasma flows again in the opposite direction through the membrane and is combined with the blood.

A similar principle is followed in WO 80/02805. Also According to this document, pressure oscillations become a part of the feed stream convectively through the membrane and back again led into the feed stream. In contrast to EP-A-0 112 094 is biological in the device according to WO 80/02805 active material to which the target substance to be treated Liquid should be bound in the pores and on the Surface of the membrane coupled to the membrane so that the substance-specific treatment of the liquid when flowing through the membrane takes place.

EP-A-0 341 413 describes an adsorber module for treatment described by whole blood, in which the with liganded hollow fiber membranes in cross-flow mode blood flows through the lumen. Here occurs Plasma as permeate through the hollow fiber membrane wall into the Hollow fiber membranes surrounding the exterior, being in the Treatment of the plasma is carried out on the membrane wall. In a In a special embodiment, this module has no outlet for the permeate, but in the treatment of whole blood the plasma separated as permeate collects outside around the capillaries and occurs as a result of the emerging Pressure conditions again through the hollow fiber membrane wall in the lumen of the hollow fiber membrane. Such a module concept has the disadvantage, however, that on the membrane passing through Plasma flow only influenced to a limited extent can be. Furthermore, the necessary ones Treatment times relatively long, because only for filling the Outside around the hollow fiber membranes permeate times of more than 10 min. required are.

The modules described, which are operated in cross-flow mode substance-specific treatment of liquids have disadvantages such as. the need for additional pumps and / or Control bodies due to separate permeate and retentate flows or additional units for generating pressure oscillations on. Common to all is the disadvantage that the membranes must always be embedded in the housing is, which makes the manufacture of the membrane modules complex becomes. This is particularly disadvantageous if the treatment process the series connection of several Requires modules. It’s also important if aggressive for coupling or polymerization of the ligands Solvents such as Toluene are used and this coupling takes place in the device. In practice it has shown that a solvent-resistant then required Embedding is very complex and involves high costs.

It is therefore an object of the invention to provide a device type mentioned for the substance-specific treatment of To provide fluids at which the named Disadvantages of the prior art are at least reduced which is easy to manufacture, which is flexible to the respective fluid treatment can be adapted and also suitable for clear solutions and especially for suspensions is.

It is a further object of the invention to provide a method of type mentioned above for efficient substance-specific treatment of fluids using semipermeable To provide membranes with a porous structure that also for the treatment of suspensions is suitable.

a) einem Gehäuse,

b) einer Einlaßeinrichtung zum Einleiten des zu behandelnden Fluids in das Gehäuse,

c) einer Auslaßeinrichtung zum Ableiten des behandelten Fluids aus dem Gehäuse,

d) mindestens einem Behandlungselement zur stoffspezifischen Behandlung des Fluids mit einem der Einlaßeinrichtung und einem der Auslaßeinrichtung zugewandten Ende und einer Wand, die zumindest teilweise aus mindestens einer semipermeablen Membran mit einer porösen Struktur gebildet ist,

wobei das mindestens eine Behandlungselement mindestens einen durch die Wand des Behandlungselements gebildeten Hohlraum aufweist, wobei der Hohlraum geschlossen oder höchstens in Richtung der Auslaßeinrichtung einseitig geöffnet ist, wobei das mindestens eine Behandlungselement derart im Gehäuse angeordnet ist, daß zwischen Einlaßeinrichtung und Auslaßeinrichtung ein durchgehendes, vom zu behandelnden Fluid durchströmbares, das mindestens eine Behandlungselement berührendes und umgebendes und das mindestens eine Behandlungselement zumindestens an seinem der Einlaßeinrichtung und an seinem der Auslaßeinrichtung zugewandten Ende im wesentlichen umschließendes Kanalsystem ausgebildet ist und wobei auf und/oder in der Membran stoffspezifisch wirkende Gruppen immobilisiert sind.The object is achieved by a device for the substance-specific treatment of a fluid by interaction with target substances contained in the fluid to be treated, the device consisting of

a) a housing,

b) an inlet device for introducing the fluid to be treated into the housing,

c) an outlet device for discharging the treated fluid from the housing,

d) at least one treatment element for substance-specific treatment of the fluid with one end facing the inlet device and one end of the outlet device and a wall which is at least partially formed from at least one semipermeable membrane with a porous structure,

wherein the at least one treatment element has at least one cavity formed by the wall of the treatment element, the cavity being closed or at most open on one side in the direction of the outlet device, the at least one treatment element being arranged in the housing in such a way that a continuous from the inlet device and outlet device fluid to be treated, through which the at least one treatment element contacts and surrounds and the at least one treatment element at least at its inlet system and at its end facing the outlet system is essentially enclosing channel system and wherein substance-specific groups are immobilized on and / or in the membrane.

a) Einleiten des zu behandelnden Fluids in das Gehäuse,

b) Durchströmen des Gehäuses mit besagtem Fluid, dabei Vorbeileiten des zu behandelnden Fluids als Primärstrom an der Außenseite der Membran, nicht jedoch an ihrer Innenseite derart, daß ein Teil dieses Primärstroms als Sekundärstrom über die Außenseite in die Membran einströmt, durch die Membran hindurchströmt, wobei an dem den Sekundärstrom bildenden Teil des zu behandelnden Fluids die stoffspezifische Behandlung des Fluids erfolgt, und anschließend durch die Innenseite aus der Membran herausströmt,

c) Ausleiten des behandelten Fluids aus dem Gehäuse,

wobei die Membran über ihre gesamte Erstreckung an ihrer Außenseite im wesentlichen frei vom Primärstrom umströmt wird und daß der durch die Membran hindurchgeströmte Sekundärstrom nach der stoffspezifischen Behandlung dem an der Außenseite der Membran strömenden Primärstrom wieder zugeführt wird.The object is further achieved by a method for the substance-specific treatment of a fluid by interaction with target substances contained in the fluid to be treated using this device, the device containing at least one treatment element which is at least partially formed from at least one semipermeable membrane with a porous structure, wherein the membrane has at least one first surface defining the outside and at least one second surface defining the inside, and wherein the method comprises at least the steps:

a) introducing the fluid to be treated into the housing,

b) flowing through the housing with said fluid, passing the fluid to be treated as a primary flow on the outside of the membrane, but not on the inside such that part of this primary flow flows into the membrane as a secondary flow through the outside, flows through the membrane, the substance-specific treatment of the fluid takes place on the part of the fluid to be treated which forms the secondary flow, and then flows out through the inside of the membrane,

c) discharging the treated fluid from the housing,

wherein the entire outer surface of the membrane is essentially free of the primary flow and the secondary flow that has passed through the membrane is fed back to the primary flow flowing on the outside of the membrane after the substance-specific treatment.

Fluids to be treated are within the scope of the present Invention to understand such fluids that certain substances or Contain target substances to which the substance-specific Treatment is targeted.

The device according to the invention is constructed in such a way that treating fluid via the inlet device into the housing is introduced and as a primary current in the housing through the Channel system in the direction of the outlet device on the in the housing arranged at least one treatment element flows past. This is at least one Treatment element in the housing of the invention Device inserted without embedding the ends which requires at least one treatment element, i.e. that of the inlet device and that of the outlet device facing ends are free of one end enclosing embedding. That is how they are Ends of the at least one treatment element in the essentially flowed around by the primary current.

Due to the generated by the flow in the canal system Part of the pressure drop along the treatment element penetrates of the primary current as a secondary current into the treatment element and flows through the semi-permeable wall of the treatment element, the substance-specific treatment in Takes place in relation to the target substance, and accumulates in the at least one cavity of the treatment element.

The caves can be closed or at most in the direction the outlet device must be open. Surprisingly It has been shown that even with closed cavities Secondary current through the treatment elements having such cavities formed. However, an embodiment is preferred the device according to the invention, in which at least a cavity toward the outlet opening has, which opens into the channel system.

In the case of the closed cavity, the secondary current occurs due to the pressure drop in the upper, the inlet device facing section of the treatment element the semipermeable wall into the element collects in the Cavity and occurs in the lower, the outlet device facing Section of the treatment element due to the reduced Pressure in the primary flow in the opposite direction from the cavity through the semipermeable wall into the Channel system from where it combines with the primary current again becomes. Here, the substance-specific treatment of the Partial flow fluid in both the first and second pass through the wall.

In the preferred case that at least one cavity in Direction of the outlet device has an opening in the channel system opens, the secondary flow occurs essentially over the entire extent of the treatment element between inlet device and outlet device in the treatment element one with a decreasing gradient of the Material flow in the direction of the outlet device. The whole through the semi-permeable, porous wall Secondary current collects in the cavity and flows at the bottom End of the element through the opening back into the duct system, where it is reunited with the primary current. This Execution of the open towards the outlet device and cavity communicating with the duct system offers the advantage that compared to a closed Cavity larger secondary currents i.e. higher flows through the wall of a treatment element, because the secondary current exits the treatment element not through the semi-permeable wall of the treatment element built up flow resistance must overcome.

The requirement of at most towards the outlet device open cavity results from applicability the device for suspensions according to the invention Task. For example, a treatment item with the cavity open towards the inlet device act like a dead-end filter, what when treating Suspensions would result in the suspended Would deposit particles in the cavity.

When dimensioning the cavity, it is important that the flow resistance which arises when the secondary current flows through the cavity is small compared to the flow resistance which arises when the semipermeable wall flows through. At the same time, it is desirable that the greatest possible proportion of the volume of the treatment element per treatment element consists of semipermeable porous membrane wall in which the substance-specific treatment takes place. A preferred ratio V _w / V _{b of} the volume of the walls of a treatment element V _w , based on the volume V _{b of} the treatment element composed of the volume of the walls V _w and the volume of the at least one cavity V _h , is in the range 0.5 <V _w / V _b <0.98, a particularly preferred ratio is in the range 0.6 <V _w / V _b <0.85.

In addition to other influencing factors, this is caused by a treatment element flowing secondary current through the along the treatment element existing pressure gradient dp / dx determined. Here dp is the differential pressure change along one differential path dx in the direction of the primary current. ever the greater this pressure gradient, the greater the secondary current through the treatment element and the larger consequently the part of the primary current that the undergoes substance-specific treatment. The pressure drop along a treatment element or along the Treatment element surrounding duct system increases with increasing Throughput through the channel system, i.e. with increasing Primary current too.

The pressure drop dp / dx increases the greater the ratio V _B / V _G , which is referred to as the degree of filling, V _{B being} the total volume of all treatment elements composed of the sum of the volumes V _{b of} the individual treatment elements and V _{G being} the volume of the empty housing. A ratio V _B / V _{G of} between 0.4 and 0.95 has proven successful, and a ratio of between 0.55 and 0.75 has proven extremely effective. At such filling levels, the distances between the treatment elements and thus the corresponding dimensions of the cross sections of the channels of the channel system become so small that, in conjunction with suitable throughputs or flow velocities in the channel system, sufficiently high pressure gradients are created to prevent diffusive transport through the porous membrane structure overlay much larger convective transport due to the secondary flow.

It is appropriate that the treatment element and its at least a cavity its longitudinal extension in the direction of the Flow through the housing. A dimensional ratio is advantageous L / D of the at least one cavity between 2 and 4000, where L is the cavity dimension in the flow direction of the housing and D the hydraulic diameter of the cavity cross section perpendicular to it. The hydraulic diameter D is defined by the relationship D = 4 * A / U with A as the area of said cross section and U as its Scope. Dimensional ratios L / D are particularly advantageous between 20 and 450.

Here, treatment elements are preferred whose walls are in its extent perpendicular to the direction of the primary flow have a substantially uniform thickness. Thereby is also achieved that the secondary flow in the flow the membrane at every point of a treatment element in the covers essentially the same flow paths, with regard to for a residence time of the patient to be treated that is as uniform as possible Fluids is of particular advantage.

In the case of the arrangement of a single treatment element in the Housing cross section, it is necessary to between the duct system Form treatment element and housing inner wall, for example by separate spacers or a corresponding one Shaping of the treatment element and / or the inner wall of the housing, being as uniform as possible The channel system also flows around the treatment element should be as uniform as possible.

In terms of treating larger amounts of fluid, it is however often useful, at least treatment elements a group of at least two, but preferably more Summarize treatment elements, the Treatment elements essentially transverse to the direction of the Extension of the channel system between the inlet device and Outlet device are arranged side by side.

It is advantageous here if the grouped together Treatment elements by spacers against each other be kept at a distance so that the treatment elements around a channel system with defined channels trains through which a uniform flow the group of treatment elements and an even Flow around the individual treatment elements is made possible. In addition, the size of the Adjust flow cross sections of the channels, which in the case an adaptation of the substance-specific treatment of suspensions the size of the particles contained in the suspension is enabled and thereby a blockage of the duct system can be prevented. At the same time, the Adjustment of the flow cross sections influence the in pressure gradients setting the channels.

The spacers are expediently designed such that they have an elastic component. As a result, a such group of treatment elements in a simple manner the housing of the device can be inserted by the Group is first slightly compressed, the Distance between the treatment elements slightly reduced is inserted into the housing and then relaxed becomes, which increases the distance between the treatment elements enlarged again. As a result, that the group of treatment elements on its outer circumference abuts the inner wall of the housing, and an undesirable Edge flow along the housing inner wall is at least reduced. A distance between the at the Housing wall adjacent treatment elements and the housing inner wall, which is less than or equal to the distance between the Treatment elements is.

The spacers can also be used as thin tubes or Capillaries should be formed, the axis of which is essentially parallel to the extent of the treatment elements of a group lies between inlet device and outlet device and which can be flowed through by primary current in their lumen. These tubes or capillaries are preferably not along the entire extent of the treatment elements arranged between inlet device and outlet device, but in a partial area of this extension on that of Outlet device facing end of the treatment elements. In this way, the pressure drop of the primary flow can be increase and thus the secondary current through the treatment elements enlarge.

Similar effects can also be achieved with a corresponding one Achieve design of the housing cross-section when the Housing cross section in the area of a step of treatment elements each tapered towards the outlet device. hereby is the distance between the treatment elements whose ends facing the outlet device relative to the Distance at the ends facing the inlet device reduced.

To increase the efficiency of the substance-specific treatment it is an advantage if in the housing towards the Extension of the duct system between the inlet device and Outlet device, i.e. in the direction of the flow of the Housing several treatment elements or groups of treatment elements are arranged as steps in a row. By connecting a large number of stages can simultaneously measure the size of the individual stage Direction of flow through the housing kept short and thereby a change in concentration with regard to possible critical Components in the fluid to be treated avoided become. This is particularly the case with such methods substance-specific treatment of suspensions of importance, in which at least part of the suspended particles pass through the semipermeable membrane wall of the treatment elements is retained should be and at the same time too high concentrations should be avoided on suspended particles, such as e.g. in the substance-specific treatment of blood. By comparatively short treatment elements will be along the Treatment elements of the primary stream only a small partial stream withdrawn, so that the concentration changes up to following merging of primary and secondary current low stay.

In the device according to the invention, the Number of stages in the housing between 1 and 1000. Has proven itself a number of steps between 1 and 100, one has proven itself Number of stages between 1 and 10. It is advantageous if the individual steps are at a distance from one another in order to neither the primary current nor the secondary current locally through the downstream in the flow direction of the housing to impose an ordered level and to ensure thorough mixing of primary current and secondary current. A uniform mixing is an advantage, e.g. undesirable Avoid fluctuations in concentration. Prefers the ratio s / D of the distance s lies between two successive ones Steps to the hydraulic diameter D of the Cavities of the treatment elements between 0 and 5.

Of course, is adapted to the needs of the treatment process also the series connection of several Devices of the invention possible, preferably contain multiple levels of treatment elements.

In the preferred embodiment of the invention, the secondary current flows through the semi-permeable wall of the treatment elements and convectively transports the target substance through the Membrane. This presupposes that the one used to form the treatment elements semipermeable membrane with porous Structure has a pore size that is convective Permits transport of the target substance through the membrane.

Given a pressure gradient in the duct system around a treatment element and given geometric dimensions of the treatment element of course the secondary current is maximized, when the average pore size of the membrane is maximized. in the Use case, the pore size must also be the size of the Target substance that is in the form of dissolved macromolecules, but also in the form of small particles with a particle size can be in the sub-micrometer range. simultaneously can it e.g. in the substance-specific treatment of Suspensions may be required that the membrane separating function takes over and contained in the suspension Holds back components that are not target substances. This means that the pore size has a certain maximum Value may not exceed. This can result in a blockage of the pore system or, for example, undesirable interactions between such restrained components intended to interact with the target substances Prevents substance-specific groups in the membrane become.

On the other hand, it can with regard to the following executed applications of the device according to the invention or embodiments of the method according to the invention Rather important are membranes with the smallest possible pore sizes and the largest possible pore volume or as large as possible Porosity to use, so for the substance-specific treatment the largest possible inner surface of the membrane to provide. They preferably have according to the invention used membranes an average porosity between 50% by volume and 90% by volume. This is called the medium porosity Ratio of the pore volume of the membrane to the membrane volume understood, where the membrane volume from the pore volume and the volume of the membrane structure Material.

The requirements for the structure of the membrane, i.e. at yours Structure and pore size distribution over the membrane thickness result from the respective application of the substance-specific Treatment. The membrane structure can over the Thickness isotropic, i.e. are within the membrane structure the pore diameters are essentially constant, they can not be isotropic, symmetrical or asymmetrical, and the membrane can have a layer on one of its sides much denser pore structure, i.e. have skin. In the case of an asymmetrical membrane, the denser Layer of the outside of the treatment element or the Cavity facing. For example, at substance-specific treatment of suspensions required be that the membrane to achieve a certain separation effect a small pore diameter at the suspension facing side. In order to have one if possible large secondary current through the membrane or the treatment element to get, however, is the remaining membrane structure expediently coarse-pored, but not depending on the application too coarse-pored to have the largest possible inner surface achieve.

Membranes with an average pore diameter are preferred between 0.005 and 5 µm, particularly preferably those with an average pore diameter between 0.1 and 3 µm used.

To determine the average pore diameter, depending on Size of the pore diameter and different depending on the membrane structure Procedure applied. For essentially isotropic Pore structures are indirectly determined by pore diameters a filtration experiment determined by an aqueous Dextran solution with a given size distribution of Dextran molecules are filtered through the membrane. From the measured relative backing as a function of nominal The pore diameter distribution becomes the molecular diameter and from this the average pore diameter is calculated. This The method is described, for example, by K. Sakai, J. Membrane Science 96 (1994), 91-130, or by Shin-ichi Nakao, J. Membrane Science 96 (1994) 131-165, for dialysis or filtration membranes described.

For non-isotropic membranes, e.g. a shift with have denser pore structure, are used to determine the average pore diameter within the denser layer likewise the cited determination methods based on Filtration experiments used. To determine the average pore diameter of the larger pored areas of the Non-isotropic membranes become an image analytical process according to L. Zeman et al., J. Membrane Science 71 (1992), 221-231 used. This is suitable for a pore size range between 0.1 µm and 5 µm, naturally both for isotropic and also for non-isotropic pore structures.

It is for applications of the device according to the invention or the method according to the invention for liquids such as in particular clear solutions or suspensions advantageous if the membrane in the direction of its extension between the channel system and the at least one cavity, i.e. perpendicular to their outer surface in at least 80% of these Extension a substantially constant mean pore diameter having. This allows a high inner Surface combined with a large number of immobilized, substance-specific groups in the membrane at the same time-low pressure loss when flowing through the Membrane perpendicular to its surface and therefore a high secondary current achieve. As an essentially constant mean pore diameter is understood to be one that no longer in the extension of the membrane mentioned changes as +/- 50%.

Proved for the substance-specific treatment of suspensions it is advantageous if a membrane is used, the a layer on its side facing the sewer system has a smaller average pore diameter than the area adjacent to the cavity the membrane with an essentially constant mean pore diameter. This layer is advantageously between 1 µm and 5 µm thick and has an average pore diameter which is 5 to 50 times smaller than the middle one Pore diameter in the adjacent area.

Porous membranes with a large inner surface are preferably used in the device according to the invention or for carrying out the method according to the invention. Porous membranes with a BET surface area between 2 and 300 m ² per cm ³ membrane volume have proven successful; membranes with a BET surface area between 4 and 30 m ² per cm ³ membrane volume have proven themselves. The BET method based on nitrogen adsorption measurement for determining the surface of porous membrane structures is described by K. Kaneko, J. Membrane Science 96 (1994), 59-89.

In the context of the present invention, hollow fiber membranes are preferred or flat membranes used to treat the treatment elements train. But there are also other membrane shapes such as. Membrane hoses or membrane tubes included.

In the case of preferred use of hollow fiber membranes the wall of the hollow fiber membrane is also the wall of the at least one cavity of the treatment element and the Hollow fiber membrane closed at least at one end. The Cavity is formed by the lumen of the hollow fiber membrane and bounded by the inside of the hollow fiber membrane.

Treatment elements can be easily made from hollow fiber membranes produce in the sense of the present invention. By closing both ends or only one end of hollow fiber membrane pieces, for example by welding, can treatment elements with closed or with the cavity open on one side. By Folding hollow fiber membrane pieces across the longitudinal axis Depending on the design, treatment elements are created with two cavities or treatment elements open on one side a cavity that faces two in the same direction Has openings. Such treatment elements are so in to bring in the housing of the device according to the invention, that the openings towards the outlet device of the device point and the treatment elements always in the direction the inlet device are closed.

Hollow fiber membranes with different outer contours, i.e. with different outer cross-sections Outlines can be used. The hollow fiber membranes For example, an essentially round or circular, triangular, square, hexagonal or octagonal Have a contour, they can also be oval, elliptical, three-lobed, be four-lobed, etc. For use in the device according to the invention or for carrying out the The method according to the invention has hollow fiber membranes proven that have a wall thickness between 15 µm and 500 µm, Hollow fiber membranes have proven their worth a wall thickness between 100 µm and 300 µm. Preferably is the hydraulic diameter of the hollow fiber membranes used 50 microns to 900 microns are particularly preferred Hollow fiber membranes with a hydraulic diameter between 200 µm and 400 µm.

The hollow fiber membranes are advantageously at least a group of adjacent treatment elements summarized, the hollow fiber membranes of such Group are kept at a distance by textile threads. in the In principle, it is sufficient to put the textile threads between the Lay hollow fiber membranes. However, the Hollow fiber membranes of a group using the textile threads in integrated at least one hollow fiber mat. Such mats can advantageously be used as a knitted mat by known methods, Woven mat or ribbon, but also as a knitting or produce as a crochet mat. In the case of weaving or The textile threads act crosswise to the hollow fiber membranes trending weaving or knitting threads. Through this The hollow fiber membranes are advantageously mutually transverse threads kept at a constant distance and within the Mats arranged essentially parallel to each other. through Such mats can be groups of side by side Manufacture treatment elements that have a high Have order and where between the treatment elements a uniform channel system is formed.

Such mats from treatment elements Hollow fiber membranes can for example be single-ply or also multilayered in a spiral in accordance with known methods be wound up or to stacks of individual mat layers or folded mat layers are stacked on top of each other. The individual windings or the individual layers expediently kept at a distance from one another, e.g. by means of the woven or knitted threads and if necessary by means of additional between the individual winding layers introduced spacers in the form of fluid-permeable Fleeces or fabrics.

The groups of hollow fiber membranes thus produced are then in the housing of the device according to the invention brought in. Here is the presence of an elastic Component of the spacers, such as in Fleeces due to a reversible compressibility of the Fleece occurs, is advantageous and facilitates the introduction of the groups in the housing. Preferably bundles are used where at least one hollow fiber mat by one Axis or a core parallel to the direction of extension of the channel system between the inlet device and outlet device the device is wound spirally. A further advantageous embodiment are bundles in which at least two hollow fiber mats placed on top of each other and around an axis or a core parallel to the direction of the mentioned extension of the channel system spirally wound are, with the hollow fiber mats superimposed are that the hollow threads of the superimposed hollow fiber mats are placed in an intersecting arrangement. The production of such bundles is described in detail in the EP 285 812. For such bundles, the can be between forming the cross-arranged hollow fiber membranes Angles between 0 ° and 120 ° are considered to be favorable Angles between 30 ° and 90 ° are highlighted.

Treatment elements can also be easily made from hollow fiber membranes with more than one cavity. Correspondingly sized hollow fiber membrane pieces can, for example, in several places along its longitudinal axis pressed together or welded, creating several closed cavities one behind the other. Similarly, you can open several Realize cavities by placing the hollow fiber membrane on several Partially along its longitudinal axis is cut, whereby - based on the in the Device installed state of a treatment element thus produced - In the direction of the outlet device lying cut edge with the remaining membrane wall is welded, so the cavities towards the inlet device close.

According to a further preferred embodiment of the invention is the at least one treatment element from at least a flat membrane is formed. Such a treatment element can be, for example, by folding a U-shaped for example, rectangular or square piece of one Produce flat membrane. The two resulting legs the U-shaped folded flat membrane are used to form the at least one cavity kept at a distance. As a spacer can be a fluid permeable material such as e.g. a fleece or a fabric can be used.

According to a further advantageous embodiment of a treatment element flat membranes become two parallel to each other and spaced apart flat membranes at least on their towards the inlet device facing edge positively connected, for example welded together so that through the flat membranes the legs of the treatment element are formed become. The two flat membranes used can be the same , but they can also be different, e.g. in the In terms of their material, structure or interaction provided with the target substances substance-specific groups. Also one of the two can Flat membranes against a fluid-impermeable one, for example Can be exchanged where this - for reasons of Stability of the treatment elements or from a manufacturing point of view - appears cheap.

With such treatment elements, the one enclosing the cavity becomes Side of the membrane or optionally used Foil as the inside and the one facing outwards Side as the outside of the membrane or, if applicable used foil defined.

The in the device according to the invention or for implementation of the flat membranes used in the method according to the invention preferably have a wall thickness between 15 microns and 500 µm, flat membranes with are particularly preferred a wall thickness between 100 µm and 300 µm.

The two closed at the folded edge or the form-fitting Edge adjacent sides of the treatment element are expediently e.g. by welding too locked. Laterally open treatment elements made of flat membranes are due to possible leakage and short-circuit currents not recommended for use. That of the folded edge opposite edge can be used to produce a closed Cavity are also closed. she stays but advantageously to produce one on one side open cavity unlocked, in which case the treatment element thus created in the housing of the The device according to the invention is to be introduced such that the opening points towards the outlet device of the housing.

Treatment elements produced in this way can be used in flat shape are used, preferably several of these planar treatment elements in groups of stacks are layered side by side. It is useful to keep your distance between the treatment elements of a group and between the housing inner wall and those adjoining it Treatment elements a material permeable to fluids such as. a fabric or fleece is used to which especially in the substance-specific treatment of Suspensions have high permeability requirements are to be asked. So this permeable material holds it Outside of the membranes and any used Foils at a distance and also builds in the direction of flow an additional pressure gradient of the primary flow, the influence on the size of the secondary current.

The spacers, as described, for a defined Distance between the legs of the at least partially treatment elements formed from flat membranes, between the treatment elements of a group as well as between Housing inner wall and adjacent treatment elements should care and at the same time be fluid permeable, can be designed as separate elements. The spacer function on the inside and / or outside of the Membrane and / or possibly connected to the membrane However, film can also be in the membrane or the film be integrated e.g. through groove-shaped, knob-shaped or other profiled surface structures.

Leave groups of treatment elements made of flat membranes for example by pleating a three-layer to produce flat laminate that consists of a flat spacer, for example in the form of a permeable fleece, a centrally located flat membrane system and another Spacer layer exists. By pleating together this three-layer laminate results in a flat pleated product, from the by subsequent, in relation to the Extension level of the pleated product e.g. cut in the middle Groups of treatment elements arranged side by side arise from U-shaped folded flat membranes. For better processing, the three layers of Laminates e.g. can also be connected to one another in a punctiform manner.

An embodiment has proven itself in which the folded edges the treatment elements of two successive stages the device according to the invention in the direction of extension of the channel system between the inlet device and outlet device seen form an angle between 5 ° and 175 °. The angles 30 °, 45 ° or 90 ° are preferred. In this way there will be better mixing between the primary and secondary currents reached after each stage and training one Edge flow between treatment elements and the inner wall of the housing reduced. The distance between the steps can be minimized and is preferably such that the ratio s / D of the distance s between two neighboring hydraulic stages Diameter D of the cavity of the treatment elements is between 0 and 1.

Treatment elements can also be easily made from flat membranes with several cavities one behind the other produce. Correspondingly in their length in the flow direction of the housing of the device according to the invention dimensioned flat membrane treatment elements can in their Longitudinal extension, for example, in several places transverse to Longitudinal extension compressed or welded together , making several closed one behind the other and cavities supported by spacers. In Similarly, several successive, Opened cavities realized in the direction of the outlet device by adding the treatment elements to several Make along its longitudinal axis transverse to this at one Thighs are cut through, and in the direction of the Cutting device lying with the cut edge Welded leg of the treatment element or is glued so the cavities towards the inlet device close.

The flat treatment elements described can be also process into spiral wound treatment elements, where, for example, about an axis or a Core perpendicular to the folded edge or positively connected Edge is wound spirally. Between each Spacers are advantageously inserted, being for the distance between the individual winding layers the same conditions apply as for the distance between two flat treatment elements made of flat membranes. Such spiral wound treatment elements are then advantageously arranged in a housing such that the direction of the winding axis and the flow direction of the Housing match. The open one, if any Edge of the spiral treatment element has thereby in the direction of the outlet device of the housing.

The shape of the inner cross section of the housing in which the Treatment elements, the treatment elements combined in groups or arranged the levels of treatment elements can be any. However, are preferred at Hollow fiber membranes and flat membranes Housing with a square, rectangular, hexagonal, octagonal or also round inner cross section used.

The treatment elements or groups are in this housing of treatment elements, which preferably have spacers have an elastic component, under a low Compression introduced and positioned in the housing with relaxation. In the case of flat treatment elements Flat membranes can vary depending on the shape of the housing cross-section easily defined angles between the folded edges of the individual steps in the housing become.

With treatment elements made of hollow fiber membranes, depending on Use also a syringe needle or a cannula as a housing be suitable, e.g. also several levels of individual treatment elements arranged one behind the other are. For other applications there is a flexible housing e.g. proven from an elastic hose. The housing can for easier introduction of the treatment elements or the Groups or stages of treatment elements also radial be designed to be shrinkable, the shrinkage after Introducing the treatment elements is made. Especially with long housings relative to their diameter it can be advantageous, the housing, for example, helical or to wrap or shape spirally.

A firm connection between the treatment elements and the housing is unnecessary in many cases. However, it is in Special cases also possible, e.g. using polyurethane, epoxy resin, Thermoplastic or the like that of the housing wall neighboring treatment elements of a group or one Level at least partially firmly with the inner wall of the housing connect. This allows for stable positioning the respective group of treatment elements be taken care of, but above all, such an undesirable Edge flow between the inner wall of the housing and treatment elements at least decrease, and inaccuracies in the The outer contour of groups of treatment elements can be balanced. Furthermore, for example, the described flat membrane treatment elements on their End faces, i.e. on the folded edge or form-fitting connected edge adjacent edges are sealed. Suitable methods, such as the treatment elements with the housing are to be connected, for example, in EP-A-521 495 described.

The method according to the invention can be used for a wide variety of substance-specific Treatments of fluids are used. in this connection are particularly good results in treatment achieved that the inventive method in these inventive methods Device is used, being on and / or Groups specific to the membrane are immobilized are. With regard to the respective treatment method can different substance-specific groups and / or immobilized in the membranes that are specific with various contained in the fluid to be treated Interact with target substances. In the same way you can different membranes, each with different substance-specific acting groups can be used together.

In a preferred embodiment of the invention The fluid to be treated is recirculated and goes through the treatment process several times until a desired one Degree of treatment is reached. As to be treated Fluids preferentially contain particle-containing suspensions Commitment.

According to a particularly preferred embodiment of the invention are the substance-specific groups Ligands for the affine separation of ligates from those to be treated Liquids, around enzymes or around catalysts. preferred Processes according to the invention are purification / separation processes ligates from a ligate-containing liquid, where membranes are selected on and / or in which Ligands for said ligates are immobilized, furthermore Process for the enzymatic treatment of liquids, wherein Membranes are selected on and / or in which enzymes are immobilized, and methods for catalytic treatment of liquids, with membranes be selected on and / or in which catalysts are immobilized are.

For the immobilization of substance-specific groups and / or in the membranes can be those described in the literature Procedures are used. Also regarding in relation to the respective substance-specific fluid treatment usable substance-specific groups can those described in the literature are used. Different ways of immobilizing the substance-specific groups come into consideration, both in terms of the place where they are immobilized as well as in Regarding the way they are immobilized.

So these substance-specific groups can be addressed to the Membrane adsorptively or coupled via covalent bonds his. This coupling to the membrane can both before installation in the housing as well as after inserting the membrane as a treatment element in the housing of the device according to the invention respectively. Here, in coordination with the respective Use case, for example, the substance-specific groups essentially homogeneous over the entire surface the porous membrane, i.e. both on the outside and on the inner surfaces formed by the pores are coupled, i.e. be immobilized on and in the membrane. It can but it may also be necessary for the substances to act Groups only immobilized on part of these surfaces are, for example if individual components of the to be treated Fluids not with the substance-specific groups should come into contact. In such a case it is expedient, on the one hand by selecting a membrane with a suitable separation limit to transport these components through the membrane to the immobilized substance-specific to avoid acting groups. On the other hand, it is also required that corresponds to the primary current, i.e. which these components containing fluid-facing surface of the membrane or the treatment element free of substance-specific Hold groups. This can be done through passivation this surface e.g. through a plasma treatment before coupling of the substance-specific groups can be reached.

However, it can also be a direct installation of substance-specific acting groups take place in the membrane matrix, in the case of Membranes made of polymeric materials, for example by modification of the polymer material with, for example, ionic, hydrophilic or hydrophobic groups or by using Polymer blends in which at least one polymer component has substance-specific groups.

Another possibility is to do such substance-specific groups or such groups having carrier substances or particles in the pore system to store a membrane in the manufacturing process of the membrane or subsequently into the finished membrane e.g. einzuschwemmen. In the latter case, the membrane expediently an asymmetrical structure and, if necessary, a Skin on, the openings of the skin or the pores of the finer pore side of the membrane are dimensioned so that the substance-specific groups or the carrier substances mentioned or particles cannot pass through. in this connection the floating and the subsequent substance-specific Fluid treatment carried out so that the material flows from the open-pored side of the membrane enter the membrane and thereby the groups bearing the substance-specific effect Substances or particles through the less open-pored side be held back. Such systems make sense with washed-in substance-specific groups used in conjunction with treatment elements that in Direction of the outlet opening of the treatment elements containing Device are open.

In any case, the pore size of the membrane used is so to choose that despite the immobilized in the pores substance-specific groups the target substances convectively of at least part of the fluid to be treated the membrane can be transported.

There are no restrictions with regard to the material from which the membrane according to the invention is constructed. Membranes made of inorganic materials such as glass, ceramic, SiO ₂ , carbon or metal, organic polymers or mixtures thereof can be used. The polymers can have a hydrophilic and / or hydrophobic character, they can be selected from the group of cellulosic polymers, such as cellulose or regenerated cellulose, modified cellulose, such as cellulose esters, cellulose ethers, amine-modified celluloses, and mixtures of cellulosic polymers from the group of synthetic polymers such as polyacrylonitrile and corresponding copolymers, polyurethane-containing polymers, polyarylsulfones and polyaryl ether sulfones, such as polysulfone or polyethersulfone, polyvinylidene fluoride, polytetrafluoroethylene, water-insoluble polyvinyl alcohols, aliphatic and aromatic polyamides, polyimides, polyetherimides, polyols, polyefins, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyols, polyefins, polyols, polyols, polyols, like , Polyvinyl chloride, polyphenylene oxide, polybenzimidazoles and polybenzimiazolones, as well as modifications, blends, mixtures or copolymers of these polymers obtained therefrom. Further polymers such as polyethylene oxide, polyhydroxyether, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol or polycaprolactone, or inorganic substances such as SiO _2, for example, can be added to these polymers or polymer mixtures. In individual cases, the membrane can also have been subjected to a surface modification, for example, in order to adjust certain properties of the membrane surface, for example in the form of certain functional groups.

Particularly good experiences have been made with membranes made from solvent-stable and pH-stable polymers, in particular with membranes made of polytetrafluoroethylene or Polyvinylidene fluoride and modifications derived therefrom, Blends, blends or copolymers. Such membranes are described for example in DE-A-39 23 128.

For the purification / separation of ligates from a ligate Liquid by means of affinity separation or affinity chromatography numerous applications are known. Under affinity chromatography are biospecific adsorptions here and also separation processes such as ion exchange chromatography, metal chelate chromatography, hydrophobic Chromatography, covalent chromatography or also direct sorption of molecules on a specific adsorbent material Roger that.

Interesting applications relate to the cleaning of monoclonal liquids, for the removal of proteases for the stabilization of biological liquids on which Collection or therapeutic removal of blood plasma components from blood plasma or whole blood, for removal pyrogens from biological or pharmaceutical liquids, on the separation of enantiomers or on the Isolation of enzymes, to name just a few examples.

Further applications can be found in the area of cell selection. Here you can make use of the feature that when Use of the device according to the invention or in the Implementation of the method according to the invention is part of the Primary current as a secondary current on the membrane-shaped wall the treatment elements to and through the walls of the treatment elements flowing. This has when using Cell suspensions have the advantage that cells are the target substance are transported convectively to the membranes and there in direct contact with e.g. on the outside of the membrane or the treatment element immobilized ligands brought, for example, a certain surface protein of the cells. Also for applications in The devices according to the invention are in the field of genetic engineering best suited for such applications e.g. a convective transport of genes to, for example Viruses or cells immobilized on and / or in the membrane should be achieved.

In the sense used here, ligands can have a non-specific, group-specific or specific effect depending on the application (see E. Klein, "Affinity Membranes", John Wiley & Sons, Inc., 1991). Such ligands are, for example, monoclonal antibodies, polyclonal antibodies, peptides, antigenic substances, glycoproteins, protein A, protein G, enzymes, receptor proteins, growth factors for cells, hormones, regulatory proteins, inhibitors, cofactors, heparin, protamine, poly-L-lysines, biotin , Avitin, amino acids such as trytophan, phenylamine, L-histidines or antibiotics. Furthermore, the ligands can also be salts such as Fe ₄ [Fe (CN) ₆ ] ₃ or dyes. However, they can also be hydrophilic groups or ionic groups in the surface of the membrane material itself or be polymers bound to the surface. By way of example, but without being limited to this, it is also possible to refer to those in WO 90/04609, WO 90/05018 and EP-A-0 565 978 or to those in E. Klein, "Affinity Membranes", John Wiley & Sons, Inc. , 1991, referenced examples.

Without exhaustively listing the possibilities here, the ligands can e.g. through surface modification the membrane are generated, they can be directly or via spacer molecules (Spacer) are bound to the surface, but they can also be connected to the tentacles or chains Surface bound, with each chain or to each Tentacle system multiple ligands can be bound.

In order to increase the capacity, in particular of ion exchange membranes, various methods known per se can be used, the number of ionic groups, ie the ligands on the pore surface of the membranes, being increased. The ligands are preferably coupled to the membrane via molecules of long-chain linear polymers, the molecules of the long-chain linear polymers carrying a plurality of ligands. The use of long-chain linear polymers, so-called tentacles, on the arms of which the ligands are located, is described, for example, by W. Müller, J. Chromatogr., Vol. 510 (1990), p. 133. The manufacture of such tentacles is described, for example, by Tsuneda and others (Biotechnol. Prog ., Vol. 10 (1994), pp. 76-81, and J. Chromatogr. Vol. A 689 (1995), pp. 211-218) and can be obtained by radiation-induced graft polymerization from a monomer containing an epoxy group, such as, for example Glycidyl methacrylate, followed by chemical conversion in SO ₃ H groups or diethylamino groups. Another process for the grafting of nitrogen-containing polymeric flat membranes, which can be used to increase the ion exchange capacity of the membrane treatment elements according to the invention, is described in EP-A-0 490 940.

Membranes with polymerizable double bonds derivatized polyamides according to DE-OS-195 01 726 are included for the device according to the invention and for Implementation of the method according to the invention is excellent suitable. These derivatized polyamides are available by reacting the polyamide in an aqueous solution with a compound that is both a polymerizable Contains double bond and an oxirane ring, and can to block polymers with improved properties be implemented.

For applications in the field of enzymatic or general Catalytic treatment of liquids can be membranes be selected on and / or in which according to known per se Methods immobilized enzymes or catalysts are.

Applications in the field of enzymatic liquid treatment are e.g. the enzymatic esterification of Ethylglycoside, the enzymatic hydrolysis of starch via Amyloglucosidase, the enzymatic hydrolysis of Enantiomers, vegetable oils, animal oils, e.g. Fish oil, or triglycerides via lipases, the enzymatic Degradation of proteins via proteinases, the breakdown of lactose in the Milk via lactase or the breakdown of blood components via appropriate enzymes such as urea via urease. Also applications as described in US-A-4 061 141 will fall under this. Other enzymes and theirs Application and possibilities of immobilization are in Ullmann's Encyclopedia of Technical Chemistry, 4th Edition, Vol. 10, pp. 475-561, Verlag Chemie, Weinheim 1975. Information on catalysts and their immobilization in Membrane structures, as also within the scope of the present Invention can be used, for example, in U.S. 4,266,026.

In the context of the invention, the cavities can be partially or be completely filled with functionaries without however, the actual collection and channel function for the secondary current get lost. Such functionaries can in simple case, as already described, in the form of a fluid permeable Fleece is present and only the function a spacer. But it can also be Nonwovens are used, in which particles are additionally introduced are, in turn, substance-specific groups such as in Wear the form of ligands or enzymes. Other examples are Fabrics or fleeces containing activated carbon or activated carbon alone. It is also conceivable to live in the cells Introduce voids during the substance-specific Treatment of a liquid suitable biologically active molecules generate or implement.

In the same way, there can be between the treatment elements spacers located other than the Spacer function itself perform other functions. So can - except on and / or in the porous membrane wall Treatment elements additionally acting substance-specific Groups can be immobilized on the spacers. The spacers are advantageously made for this purpose the same polymer or family of polymers as the membrane material. Especially for those between treatment elements made of flat membranes and between the mats of hollow fiber membrane elements inserted spacers proven textile fabrics, as e.g. by Y. Yang et al., J. Chromatographie 598 (1992), 169-180 become. Fabrics with multifilament threads lead with one Single thread diameter between 1 µm and 30 µm too special good results. Fabrics have also proven themselves, both the weft as well as the warp threads at an angle to the direction of the primary current have a value between 30 ° and 60 °. The spacers on the primary current side can also differ from those in the cavities and e.g. less when using suspensions be tightly woven.

Fig. 1:

Ausführungsform eines Behandlungselements mit geschlossenem Hohlraum aus einer Hohlfasermembran, verschweißte Enden

Fig. 2:

Ausführungsform eines Behandlungselements mit geschlossenem Hohlraum aus einer Hohlfasermembran, in haarnadelförmige Bögen gelegt

Fig. 3:

Ausführungsform eines Behandlungselements aus einer Hohlfasermembran mit mehreren hintereinanderliegenden geschlossenen Hohlräumen

Fig. 4:

Ausführungsform eines Behandlungselements aus einer Hohlfasermembran mit einseitig geöffnetem Hohlraum, dessen eines Ende verklebt ist

Fig. 5:

Ausführungsform eines Behandlungselements aus einer Hohlfasermembran mit einseitig geöffnetem Hohlraum, dessen eines Ende verschweißt ist

Fig. 6:

Ausführungsform eines Behandlungselements aus einer Hohlfasermembran mit einseitig geöffnetem Hohlraum, hergestellt durch haarnadelförmiges Biegen eines Hohlfasermembranstücks

Fig. 7:

Ausführungsform eines Behandlungselements aus einer Hohlfasermembran mit mehreren hintereinanderliegenden, einseitig geöffneten Hohlräumen

Fig. 8

Gruppe von nebeneinander angeordneten und in einer Matte eingebundenen Behandlungselementen aus Hohlfasermembranen mit einseitig geöffneten Hohlräumen

Fig. 9

Bündel aus einer spiralförmig gewickelten Matte von Behandlungselementen aus Hohlfasermembranen

Fig. 10

Geschlossenes Behandlungselement (Segment) aus einer wendelförmig um eine horizontale Achse gelegten Hohlfasermembran, Querschnitt

Fig. 11:

Geschlossenes Behandlungselement (Segment) aus einer wendelförmig um eine vertikale Achse gelegten Hohlfasermembran mit abgeflachtem Querschnitt

Fig. 12:

Ebenes, einseitig geöffnetes Behandlungselement aus einer U-förmig gefalteten Flachmembran

Fig. 13:

Aufeinanderfolgende Stufen aus Gruppen von U-förmig gefalteten Flachmembranen, im Winkel von 90° gegeneinander gedreht

Fig. 14:

Querschnitt durch eine erfindungsgemäße Vorrichtung

The invention is explained below with reference to the drawings. In a simplified schematic representation, they show:

Fig. 1:

Embodiment of a treatment element with a closed cavity made of a hollow fiber membrane, welded ends

Fig. 2:

Embodiment of a treatment element with a closed cavity made of a hollow fiber membrane, placed in hairpin-shaped arches

Fig. 3:

Embodiment of a treatment element made of a hollow fiber membrane with a plurality of closed cavities one behind the other

Fig. 4:

Embodiment of a treatment element made of a hollow fiber membrane with a cavity open on one side, one end of which is glued

Fig. 5:

Embodiment of a treatment element made of a hollow fiber membrane with a cavity open on one side, one end of which is welded

Fig. 6:

Embodiment of a treatment element made of a hollow fiber membrane with a cavity open on one side, produced by hairpin-shaped bending of a piece of hollow fiber membrane

Fig. 7:

Embodiment of a treatment element made of a hollow fiber membrane with several successive, one-sided open cavities

Fig. 8

Group of treatment elements arranged next to each other and integrated in a mat made of hollow fiber membranes with cavities open on one side

Fig. 9

Bundle of a spirally wound mat of treatment elements made of hollow fiber membranes

Fig. 10

Closed treatment element (segment) made of a hollow fiber membrane placed in a helix around a horizontal axis, cross section

Fig. 11:

Closed treatment element (segment) made of a hollow fiber membrane with a flattened cross-section placed around a vertical axis

Fig. 12:

Flat treatment element, open on one side, made of a U-shaped flat membrane

Fig. 13:

Successive steps from groups of U-shaped folded flat membranes, rotated against each other at an angle of 90 °

Fig. 14:

Cross section through a device according to the invention

Figures 1 to 3 show different embodiments of Treatment elements that can be produced from hollow fiber membranes are and have closed cavities. Here is in FIG. 1 shows an element shown partially in section, that from an appropriately sized piece of a Hollow fiber membrane by welding the two ends 1 of this Piece was produced. The cavity 2 is through the lumen the hollow fiber membrane, the wall 3 of the treatment element is also the wall of the hollow fiber membrane. Through the Arrows indicate the primary current 4 and the secondary current 5. The primary stream 4 runs in the direction of Longitudinal extension of the treatment element, the secondary current 5 occurs in the upper, opposite to the primary current direction Part of the treatment element into the treatment element, is collected in cavity 2 and occurs in the lower part of the Treatment element in the direction of the primary current from the treatment element out.

The treatment element according to FIG. 2 can consist of one Hollow fiber membrane can be obtained several times in a row was placed in hairpin-shaped arches. In this example are the ends of the hollow fiber element with a closure 6 provided as e.g. by dipping the ends in one Obtain casting compound or by filling with a hot melt adhesive can be. Of course, the ends are also closed possible by welding. The cavity 2 extends in the illustrated case over the entire length of the hollow fiber membrane piece. In a similar manner, however, treatment elements can also be used by kinking the hollow fiber membrane on the Make the arches so that they are then on the kinks have closed partial cavities. As for that Treatment element in Figure 1 are also for this treatment element 2 primary current 4 and secondary current 5 shown.

The embodiment shown in Figure 3 is an example for a treatment element with several in the direction of the primary current closed cavities one behind the other 2. Such an element can be welded, for example a correspondingly dimensioned hollow fiber membrane piece produce at several points 7 along its longitudinal axis.

Various embodiments are shown in FIGS. 4 to 7 of hollow fiber membrane treatment elements with one-sided open Cavities shown, these treatment elements to be installed in a housing according to the invention, that the opening 8 of the cavities open on one side in Direction of the outlet opening, i.e. in the direction of the flow of the housing through the primary current 4. The embodiment according to Figure 4 can be made from correspondingly long Pieces of hollow fiber membranes by closing one End of the hollow fiber membrane piece with a closure 6 e.g. using a hot melt adhesive or by dipping the end make into a casting compound. The embodiment in FIG. 5 represents a substantially similar element in which however, one end 1 was closed by welding. When installed, part of the primary current 4 flows as Secondary current 5 along substantially the entire length of these treatment elements through the membrane wall 3, collects open in the direction of flow through the housing Cavity 2 and leaves at the bottom through the opening 8 the treatment element.

The treatment element shown in Figure 6 is by hairpin-shaped bending of a hollow fiber membrane piece obtained and has two in the specified flow direction of the Primary flow 4 openings 8 and a continuous partially opened cavity 2 with two halves corresponding to the Halves of the treatment element. Contrary to the specified The direction of flow of the primary stream 4 is the cavity closed. Instead of a hairpin-shaped bow, too a kink in the hollow fiber membrane piece conceivable, whereby two separate cavities that are open on one side arise.

The embodiment shown in FIG. 7 represents a treatment element with several partially opened in a row Cavities 2 represents. These cavities can be by partially cutting the hollow fiber membrane on several Establish places along their longitudinal axis, the A cut edge 9 intersects the opening 8 of a Cavity, the other cut edge by e.g. Glue or Welding to the wall of the hollow fiber membrane that has remained a closure 10 of the adjacent end of the adjacent one Forms cavity. Here is how to proceed that all openings 8 of such a treatment element in the point in the same direction and all closed ends of the Cavities in the opposite direction.

Figure 8 shows schematically a group of arranged side by side Treatment elements 11 made of hollow fiber membranes open cavities on one side, which by means of textile Threads 12 are embedded in a mat. Such a mat can be, for example, by known methods Make weaving or knitting. Take over the textile threads 12 the function of spacers, and the hollow fiber membrane treatment elements 11 are substantially arranged parallel to each other. In the example shown is the flow direction of the primary stream 4 facing End of the hollow fiber membranes 11 with a closure 6 Mistake. But it can also e.g. by welding the ends or by an arc between two adjacent hollow fiber membrane elements 6 are closed.

Such a mat can be wound by spiraling this mat is bundled around an axis or a core Manufacture group of treatment elements as they do is shown schematically in FIG. In this example the mat is around a core A parallel to the hollow fiber membranes spirally wound, with only the outer Winding position is drawn. The continuation for the further inside winding layers is characterized by a spiral, through the axes of the hollow fiber membranes arranged inside the bundle dashed line. The the textile threads 12 connecting the hollow fiber membranes 11 hold both those lying next to each other in the mat Hollow fiber membranes as well as those in neighboring winding layers adjacent hollow fiber membranes at a distance. at such a structure of groups of treatment elements can be a high order of treatment elements and high and uniform filling levels of the device according to the invention realize.

In Fig. 10 is a treatment element made of a hollow fiber membrane shown, which a closed cavity 2nd has and easily by helical Winding a hollow fiber membrane 13 around a horizontal axis or, as shown, can produce a plane E, the an extension is shown by the dashed line and its longitudinal extension perpendicular to the plane of the drawing runs. The section of the Spiral lying in the plane of the drawing. Further turns close in the longitudinal direction perpendicular to the plane of the drawing on. There is preferably between the individual Turns of the spiral a distance, so that at the later application a good flow around the treatment element forming hollow fiber membrane is guaranteed. The Ends of the hollow fiber membrane are closed, so that overall along the helix over the entire length of the Hollow fiber membrane extending through cavity 2 is formed. In use, this becomes helical Treatment element arranged in the housing so that the axis the coil or the plane E around which this coil is wound was, in its longitudinal extension transverse to the direction of the Flow through the housing is aligned. This flows the secondary current in the opposite direction to the Part of the coil oriented through the primary current through the wall 3 the hollow fiber membrane in the cavity 2 of the treatment element and leaves the treatment element via the in Direction of the flow of the primary current oriented part.

Such a helical treatment element can be in a further step spirally about an axis perpendicular to the axis of the coil or perpendicular to the longitudinal extension of the Wind up the layer around which the coil is wound. This spiral wound treatment element can then in a Housing introduced with a suitably round cross-section be that the axis of the spiral towards the Longitudinal axis of the housing has.

FIG. 11 shows a further embodiment of one of a Hollow fiber membrane manufactured treatment element with a closed Cavity. This is essentially the structure of this Treatment element similar to that shown in Figure 10, i.e. the hollow fiber membrane is also helical here an axis or wrapped around a plane parallel to Direction of the primary current 4, with the ends of the Helix-building hollow fiber membrane are closed. exemplary is in the embodiment according to FIG. 11 a hollow fiber membrane flattened in cross section. In FIG. 11 there are cutouts from two adjacent ones Turns 14 of the spiral shown, wherein the cavity cross sections visible in the sectional view cross sections due to the helical structure of the element of the same cavity 2.

The installation of this treatment element in a housing In contrast to the device according to the invention Treatment element according to Figure 10 such that the axis of the Helix or the longitudinal extent of the plane around which the hollow fiber membrane is wound helically, in the direction of Longitudinal axis of the housing and thus in the direction of the flow of the housing points. This essentially happens to a cross flow of the individual turns of the helix through the primary stream 4. The secondary stream 5 penetrates through the oriented opposite to the direction of the primary current Part of the flattened hollow fiber membrane in the treatment element one that collects in the entire length of the hollow fiber membrane extending cavity and occurs on the in Flow direction of the primary stream 4 oriented side of the flattened hollow fiber membrane from the treatment element. At the same time arises due to the total extent of the treatment element along its winding axis in the cavity of the Treatment element a flow in the direction of the longitudinal extent the hollow fiber membrane.

Such a treatment element can also be developed, e.g. several layers of helically wound around an axis Hollow fiber membranes concentrically one above the other be arranged, the individual layers e.g. by means of suitable spacers at a distance from each other be kept to ensure the best possible flow around the to achieve individual layers of hollow fiber membranes. Another option is to have at least one hollow fiber membrane in several layers around each other in a spiral an axis or to wrap around a core, being inside one layer the at least one hollow fiber membrane is helical is wound around the axis or around the core.

In Figure 12 is a treatment element made of a flat membrane shown, which for example by U-shaped folding of a rectangular piece of a flat membrane is obtained. The two legs 15 and 16 of the folded flat membrane are by a spacer - not shown here e.g. in the form of a liquid-permeable fleece kept apart from each other. The cavity 2 of this treatment element is through the thighs of the Flat membrane treatment element, the folded edge and the - nicht interconnected side edges, not shown here limited and points at the opposite of the folded edge Page an opening 8. The cavity 2 facing Side of the flat membrane represents the inside 17, the other side of the flat membrane represents the outside 18. In the application flows around the primary stream 4 such a treatment element from its folded edge on the outside. The secondary current 5 essentially occurs from the outside over its entire extent into the membrane wall 3 a, collects in the cavity 2 of the treatment element and occurs on the open side 8 of the cavity in the direction of Flow through the housing containing this treatment element from the treatment element as a treated secondary flow out.

Figure 13 shows two successive stages 19 of groups from stacked, U-shaped, flat flat membrane treatment elements. In this Examples are the folded edges of the treatment elements of the neighboring ones Steps turned 90 ° against each other. This can there is no need for a spacer between the steps, with a good mixing of primary current and secondary current is guaranteed. The treatment elements point between the legs for fluids forming them permeable spacers 20; the neighboring treatment elements within a stage are also through spacers 21 permeable to fluids kept at a distance, the free flow around the treatment elements to be reached on the outside through the primary stream 4.

In Figure 14 is a plurality of stages 22 of treatment elements device according to the invention containing schematically shown in cross section. The fluid to be treated enters as a feed stream 23 through the inlet device 24 into the Housing 25 of the device according to the invention and will if necessary supported by an appropriately designed - Not shown here - distribution device on the treatment elements the first stage evenly distributed. The Fluid then passes through the housings one after the other Levels 22 of treatment elements in which the substance-specific treatment of the fluid takes place. neighboring In this example, stages are indicated for the one to be treated Spacers 26 permeable to fluid at a distance from one another held to in before the fluid to be treated entered the next stage is a good mixing of primary current and To achieve secondary current. After going through the required Number of stages 22, the treated fluid 27 is over the outlet device 28 is derived from the housing.

Claims (47)

1. Device for the substance-specific treatment of a fluid by interaction with target substances contained in the fluid to be treated, consisting of

   a) a casing (25),

   b) an inlet arrangement (24) for introducing the fluid to be treated (23) into the casing (25),

   c) an outlet arrangement (28) to remove the treated fluid (27) from the casing (25),

   d) at least one treatment element for the substance-specific treatment of the fluid with one end facing the inlet arrangement and the other facing the outlet arrangement and a wall (3) that is at least partially formed from at least one semipermeable membrane with a porous structure,

   wherein the at least one treatment element has at least one cavity (2) formed by the wall (3) of the treatment element, wherein the cavity is closed, or open at most at the end facing the outlet arrangement (28), wherein the at least one treatment element is arranged in the casing (25) in such a manner that between the inlet arrangement (24) and the outlet arrangement (28) there is a continuous channel system, through which the fluid to be treated can flow, touching and surrounding the at least one treatment element, and essentially enclosing the at least one treatment element at least at its end facing the inlet arrangement and at its end facing the outlet arrangement, and wherein groups acting in a substance-specific manner are immobilized on and/or in the membrane.
2. Device in accordance with Claim 1, wherein at least one cavity (2) has in the direction of the outlet arrangement (28) an opening (8) which leads into the channel system.
3. Device in accordance with one or more of Claims 1 or 2, characterized in that at least one cavity (2) has a ratio L/D of its dimension L in the direction of the extent of the channel system between the inlet arrangement (24) and the outlet arrangement (28) and the hydraulic diameter D of its cross-section perpendicular to it of between 2 and 4000.
4. Device in accordance with one or more of Claims 1 to 3, characterized in that the at least one treatment element has a ratio V_w/V_t of the volume of its wall (3) V_w to the volume of the treatment element V_t comprising the volume of the wall (3) V_w and the volume of the at least one cavity (2) V_c between 0.5 and 0.98.
5. Device in accordance with one or more of Claims 1 to 4, characterized in that the walls (3) of each treatment element have an essentially uniform thickness.
6. Device in accordance with one or more of Claims 1 to 5, characterized by at least one group of several treatment elements, which treatment elements are arranged side by side essentially transverse to the direction of the extent of the channel system between the inlet arrangement (24) and the outlet arrangement (28).
7. Device in accordance with Claim 6, characterized in that the treatment elements put together into at least one group are kept apart from one another by spacers.
8. Device in accordance with Claim 7, characterized in that the treatment elements arranged in the casing (25) and adjacent to the inner wall of the casing (25) are at a distance from the inner wall of the casing which is less than or equal to the distance between the treatment elements.
9. Device in accordance with one or more of Claims 1 to 8, characterized in that several treatment elements or groups of treatment elements are arranged as stages (22) one behind the other in the casing (25) in the direction of the extent of the channel system between the inlet arrangement (24) and the outlet arrangement (28).
10. Device in accordance with Claim 9, characterized in that the number of stages is between 1 and 1000.
11. Device in accordance with Claim 10, characterized in that the number of stages is between 2 and 100.
12. Device in accordance with one or more of Claims 1 to 11, characterized in that the ratio V_T/V_C of the total volume V_T of all treatment elements comprising the sum of the volumes V_t of the single treatment elements and the volume V_C of the empty casing (25) is between 0.4 and 0.95.
13. Device in accordance with Claim 12, characterized in that the ratio is between 0.55 and 0.75.
14. Device in accordance with one or more of Claims 1 to 13, characterized in that the membrane has an average pore diameter between 0.005 µm and 5 µm.
15. Device in accordance with Claim 14, characterized in that the membrane has an average pore diameter between 0.1 µm and 3 µm.
16. Device in accordance with one or more of Claims 1 to 15, characterized in that the membrane has an essentially constant average pore diameter along at least 80% of its extent in the direction of its extent between the channel system and the at least one cavity (2).
17. Device in accordance with Claim 16, characterized in that the membrane has a layer on the side facing the channel system that has a smaller average pore diameter than the adjacent region of the membrane in the direction of the at least one cavity (2).
18. Device in accordance with Claim 17, characterized in that the layer is between 1 µm and 5 µm thick.
19. Device in accordance with one or more of Claims 17 or 18, characterized in that the average pore diameter in the layer is smaller by a factor of 5 to 50 than that in the adjacent region.
20. Device in accordance with one or more of Claims 1 to 19, characterized in that the membrane has an average porosity between 50 and 90% by volume.
21. Device in accordance with one or more of Claims 1 to 20, characterized in that the membrane has a BET surface between 2 and 300 m² per cm³ of membrane volume.
22. Device in accordance with Claim 21, characterized in that the membrane has a BET surface between 4 and 30 m² per cm³ of membrane volume.
23. Device in accordance with one or more of Claims 1 to 22, characterized in that the membrane is a hollow-fiber membrane and the wall (3) of the hollow-fiber membrane is the wall of the at least one cavity (2) and the hollow-fiber membrane is closed at least at one end.
24. Device in accordance with Claim 23, characterized in that the hollow-fiber membranes of a group of treatment elements (11) lying side by side are kept apart with textile threads (12).
25. Device in accordance with Claim 24, characterized in that the hollow-fiber membranes of a group are bound into at least one hollow-fiber mat by means of the textile threads (12).
26. Device in accordance with Claim 25, characterized in that the at least one hollow-fiber mat is a woven mat.
27. Device in accordance with Claim 25, characterized in that the at least one hollow-fiber mat is a knitted mat.
28. Device in accordance with Claim 25, characterized in that the at least one hollow-fiber mat is a woven tape.
29. Device in accordance with one or more of Claims 25 to 28, characterized in that the at least one hollow-fiber mat is spirally wound around an axis parallel to the direction of the extent of the channel system between the inlet arrangement (24) and the outlet arrangement (28).
30. Device in accordance with one or more of Claims 25 to 28, characterized in that at least two hollow-fiber mats are laid on top of each other and spirally wound around an axis parallel to the direction of the extent of the channel system between the inlet arrangement (24) and the outlet arrangement (28) and the hollow-fiber mats are laid on top of each other in such a way that the hollow fibers of the hollow-fiber mats laid on top of each other are brought into a criss-cross arrangement.
31. Device in accordance with one or more of Claims 1 to 22, characterized in that the at least one treatment element is formed from at least one flat membrane.
32. Device in accordance with Claim 31, characterized in that the at least one treatment element is formed from a flat membrane folded in a U-shape, wherein the fold edge formed by folding is arranged in the direction of the inlet arrangement (24) and wherein the arms (15) (16) of the flat membrane folded in a U-shape thus produced are kept apart in order to form the at least one cavity (2).
33. Device in accordance with Claim 31, characterized in that the at least one treatment element is formed from two flat membranes parallel to each other and kept apart from each other, wherein the two flat membranes are joined together positively at least at the edge they have facing in the direction of the inlet arrangement (24).
34. Device in accordance with one or more of Claims 31 to 33, characterized in that the at least one flat membrane is spirally wound around an axis parallel to the direction of the extent between the inlet arrangement (24) and the outlet arrangement (28) in such a manner that the closed edge faces in the direction of the inlet arrangement (24), wherein the laps are kept apart by spacers and by this means channels are formed between the laps, which are part of the channel system.
35. Device in accordance with one or more of Claims 1 to 34, characterized in that the membrane consists of polytetrafluoroethylene or polyvinylidene fluoride or modifications, blends, mixtures, or copolymers obtained from them.
36. Device in accordance with one or more of Claims 1 to 35, characterized in that the groups with a substance-specific action are ligands for affinic separation of ligates from the liquid to be treated.
37. Device in accordance with Claim 36, characterized in that the ligands are coupled to the membrane via molecules of long-chain linear polymers, whereby the molecules of the long-chain linear polymers carry a plurality of ligands.
38. Device in accordance with one or more of Claims 1 to 35, characterized in that the groups with a substance-specific action are enzymes.
39. Device in accordance with one or more of Claims 1 to 35, characterized in that the groups with a substance-specific action are catalysts.
40. Process for the substance-specific treatment of a fluid by interaction with target substances contained in the fluid to be treated and using a device in accordance with one or more of Claims 1 to 35, containing at least one treatment element that is at least partially formed from at least one semipermeable membrane with a porous structure, wherein the membrane has at least a first surface defining its exterior and at least a second surface defining its interior, comprising at least the steps:

    a) Feeding the fluid to be treated into the casing,

    b) Causing the same fluid to flow through the casing, wherein the fluid to be treated is caused to flow along the exterior of the membrane as a primary stream but not along its interior, in such a way that a part of this primary stream flows as a secondary stream into the membrane via the exterior, through the membrane, wherein the substance-specific treatment of the fluid takes place on the part of the fluid to be treated which forms the secondary stream, and then flows out through the interior of the membrane,

    c) Removal of the treated fluid from the casing,

    wherein the primary stream flows essentially freely along the exterior of the membrane over its entire extent and the secondary stream having passed through the membrane is reunited after the substance-specific treatment with the primary stream flowing along the exterior of the membrane.
41. Process in accordance with Claim 40, characterized in that the fluid to be treated is a suspension.
42. Process in accordance with one or more of Claims 40 or 41, characterized in that several treatment elements or groups of treatment elements are arranged in the device as stages spatially arranged one behind the other in the direction of the flow through the casing, and the fluid stream containing the primary stream and secondary stream is mixed between the individual stages.
43. Process in accordance with one or more of Claims 40 to 42, characterized in that several casings with treatment elements arranged in them are arranged one behind the other.
44. Process in accordance with one or more of Claims 40 to 43, characterized in that the fluid to be treated is recirculated.
45. Process in accordance with one or more of Claims 40 to 44 for the purification/separation of ligates from a liquid containing ligates by means of affinity, characterized in that a membrane is selected on and/or in which ligands for the aforementioned ligates are immobilized.
46. Process in accordance with one or more of Claims 40 to 44 for the enzymatic treatment of a liquid, characterized in that a membrane is selected on and/or in which enzymes are immobilized.
47. Process in accordance with one or more of Claims 40 to 44 for the catalytic treatment of fluids, characterized in that a membrane is used on and/or in which catalysts are immobilized.

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